Preserving musculoskeletal health through resistance training in individuals undergoing Glucagon-like Peptide-1 Receptor Agonist Therapy: a controlled interrupted time-series analysis (Stage 1 Registered Report)

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1-RAs) are increasingly prescribed for weight loss and cardiometabolic health but have been evidenced to lead to loss of lean soft tissue mass. Resistance training (RT) is known to result in increase muscle mass, and indeed preserve muscle mass during weight loss through more traditional weight loss approaches such as energy restriction and bariatric surgery. Yet, its effectiveness in counteracting GLP-1-RA–associated lean soft tissue mass loss remains unclear. This Stage 1 Registered Report outlines a quasi-experimental, retrospective, controlled interrupted time-series analysis using existing data from Kieser Australia members undergoing standardized RT intervention. Participants identified by internal survey to have also been on, or are currently on, GLP-1-RA therapy will be propensity score–matched to controls not receiving the drug. The primary outcome is fat free mass (via bioelectrical impedance analysis), serving as a proxy for lean soft tissue mass. We hypothesize that the effect of RT over time will be non-inferior to the effect of GLP-1-RA, indicating mitigation of lean mass loss. Secondary exploratory outcomes include effects on muscle strength. Simulations regarding estimates of GLP-1-RA treatment use in the Kieser Australia membership suggest we will be able to obtain a sample size of 37 [interquartile range: 8] matched participants per group and that, using additive estimates of the effects of RT and GLP-1-RA treatments from prior meta-analyses suggest adequate we will achieved at least 80% power at an alpha of 0.05 for testing non-inferiority with this sample size. Results will inform clinical strategies to preserve musculoskeletal health during pharmacological weight loss interventions.